{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:48:52Z","timestamp":1790102932668,"version":"4.0.1"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,5,27]],"date-time":"2013-05-27T00:00:00Z","timestamp":1369612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:p>Recent studies have demonstrated that kisspeptin (<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p) administration, given as a slow constant infusion of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 (the shortest endogenous form of the Kp molecules which carries biological activity), is able to stimulate gonadotrophin secretion and induce ovulation in anoestrus acyclic ewes. Detailed analysis of peripheral luteinising hormone (<jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content>) concentrations, obtained at 10\u2010min intervals, suggested that this <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 treatment induced the continuous release of gonadotrophins. Whether this apparent constant secretion of <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> resulted from a continuous elevation of <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> or discrete high\u2010frequency pulses could not be determined. In the present study, we monitored the patterns of gonadotrophin\u2010releasing homrone (<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH)<\/jats:styled-content> secreted into hypophyseal portal blood (<jats:styled-content style=\"fixed-case\">HPB<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> in the peripheral circulation when <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 was administered either as discrete pulses or by means of a continuous infusion. Samples of <jats:styled-content style=\"fixed-case\">HPB<\/jats:styled-content> and peripheral blood were obtained at 2 and 10\u2010min intervals, respectively, over a 6\u2010h period, from anoestrous acyclic ewes that received an i.v. bolus injection of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 at 1\u00a0h and an infusion of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 between hours 2 and 6. <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> release following <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 administration appeared to be dose\u2010dependent, with larger responses being seen to the 20 \u03bcg bolus and 20\u00a0\u03bcg\/h infusion than to the 10\u00a0\u03bcg bolus and 10\u00a0\u03bcg\/h infusion, with the latter being marginally effective in inducing <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> release. Bolus injections of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 (either 20 or 10\u00a0\u03bcg) induced a sharp <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> pulse in <jats:styled-content style=\"fixed-case\">HPB<\/jats:styled-content> and a discrete <jats:styled-content style=\"fixed-case\">LH<\/jats:styled-content> pulse in peripheral blood. By contrast, constant infusion of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 (either 20 or 10\u00a0\u03bcg\/h for 4\u00a0h) induced a sustained increase in baseline <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> secretion with no convincing evidence of strictly episodic release. Values remained continuously elevated in <jats:styled-content style=\"fixed-case\">HPB<\/jats:styled-content>. No sign of pituitary desensitisation was observed at either concentration. Finally, i.v. injection of a large bolus (500\u00a0\u03bcg) of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 produced immediate pharmacological concentrations of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 in the peripheral circulation but were not associated with detectable levels of the peptide in the cerebrospinal fluid. In summary, our results demonstrate that the mode of <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p10 administration (pulsatile versus continuous) is important in shaping the pattern of <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> secretion and suggests that this regulatory effect is most likely exerted at the level of the terminals of <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> neurones. Moreover our data also suggest that <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>p is involved in, rather than having a permissive role in, the control of endogenous <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>n<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> pulsatility.<\/jats:p>","DOI":"10.1111\/jne.12030","type":"journal-article","created":{"date-parts":[[2013,2,7]],"date-time":"2013-02-07T12:50:00Z","timestamp":1360241400000},"page":"537-546","source":"Crossref","is-referenced-by-count":46,"title":["Gonadotrophin\u2010Releasing Hormone Release into the Hypophyseal Portal Blood of the Ewe Mirrors Both Pulsatile and Continuous Intravenous Infusion of <scp>K<\/scp>isspeptin: An Insight into <scp>K<\/scp>isspeptin's Mechanism of Action"],"prefix":"10.1111","volume":"25","author":[{"given":"A.","family":"Caraty","sequence":"first","affiliation":[{"name":"UMR 7247 Physiologie de la Reproduction et des Comportements (INRA\/CNRS\/Universit\u00e9 Tours\/Haras Nationaux) Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Lomet","sequence":"additional","affiliation":[{"name":"UMR 7247 Physiologie de la Reproduction et des Comportements (INRA\/CNRS\/Universit\u00e9 Tours\/Haras Nationaux) Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. E.","family":"S\u00e9bert","sequence":"additional","affiliation":[{"name":"UMR 7247 Physiologie de la Reproduction et des Comportements (INRA\/CNRS\/Universit\u00e9 Tours\/Haras Nationaux) Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Guillaume","sequence":"additional","affiliation":[{"name":"UMR 7247 Physiologie de la Reproduction et des Comportements (INRA\/CNRS\/Universit\u00e9 Tours\/Haras Nationaux) Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Beltramo","sequence":"additional","affiliation":[{"name":"UMR 7247 Physiologie de la Reproduction et des Comportements (INRA\/CNRS\/Universit\u00e9 Tours\/Haras Nationaux) Nouzilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. P.","family":"Evans","sequence":"additional","affiliation":[{"name":"Institute of Biodiversity, Animal Health and Comparative Medicine College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1834399100"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035322"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000095549"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.111.091538"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0431"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1111\/j.1439-0531.2008.01158.x","article-title":"Basic aspects of the control of GnRH and LH secretions by kisspeptin: potential applications for better control of fertility in females","volume":"43","author":"Caraty A","year":"2008","journal-title":"Reprod Domest Anim"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409330102"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335998"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0554"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.20240"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1397"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1261"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-10-0467"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.20255"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90240.2008"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.domaniend.2010.01.001"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000318049"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1550"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0820263"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-0195"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1487"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0231"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-3046"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1282"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0089"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.130.1.1727719"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000054296"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.8.3452"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0730173"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1425"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.130.5.1572305"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.2527\/1998.7641216x"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1159\/000083140"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3328-05.2005"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0787"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2006.01420.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1636"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-1225"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2011.02199.x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1228"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.4.1603"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.12.5511"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1701"},{"key":"e_1_2_6_45_1","first-page":"????","article-title":"Kisspeptin restores pulsatile LH secretion in patients with neurokinin B signaling deficiencies. Physiological, pathophysiological and therapeutic implications","author":"Young J","year":"2012","journal-title":"Neuroendocrinology"},{"key":"e_1_2_6_46_1","first-page":"????","article-title":"Exploring the pathophysiology of hypogonadism in men with type 2 diabetes: Kisspeptin\u201010 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism","author":"George JT","year":"2012","journal-title":"Clin Endocrinol (Oxf)"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.09.020"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0022"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5848-09.2010"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00517.2010"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1159\/000329045"}],"container-title":["Journal of Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjne.12030","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjne.12030","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jne.12030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T06:46:39Z","timestamp":1698648399000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jne.12030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,27]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2013,6]]}},"alternative-id":["10.1111\/jne.12030"],"URL":"https:\/\/doi.org\/10.1111\/jne.12030","archive":["Portico"],"relation":{},"ISSN":["0953-8194","1365-2826"],"issn-type":[{"value":"0953-8194","type":"print"},{"value":"1365-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,27]]}}}